Application of microdialysis to evaluate the efflux transport of estradiol 17-β glucuronide across the rat blood-retinal barrier

The purpose of the present study was to evaluate vitreous humor/retina-to-blood efflux transport in rats and determine the efflux transport of estradiol 17-beta glucuronide (E17 beta G) across the blood-retinal barrier (BRB) by the use of microdialysis. [H-3]E17 beta G and [C-14]D-mannitol, which were used as a model compound for amphipathic organic anions and a bulk flow marker, respectively, were injected into the vitreous humor of rat eye, and a microdialysis probe was placed in the vitreous humor. [H-3]E7 beta G and [C-14]D-mannitol were bi-exponentially eliminated from the vitreous humor after vitreous bolus injection. The elimination rate constant of [H-3]E17 beta G during the terminal phase was 1.9-fold greater than that of [C-14]D-mannitol and reduced the level of [C-14]D-mannitol in the retinal presence of 0.3 mM E17 beta G, suggesting that [H-3]E17 beta G is transported via a carrier-mediated efflux transport process across the BRB. The efflux transport of [H-3]E17 beta G was significantly inhibited by organic anions, such as probenecid, sulfobromophthalein, digoxin, and dehydroepiandrosterone sulfate, whereas it was not inhibited by p-aminohippuric acid. In conclusion, the efflux transport of [H-3]E17 beta G across the rat BRB was evaluated by microdialysis and its inhibition by organic anions suggests organic anion transporting polypeptide 1a4-mediated E17 beta G efflux transport at the BRB. (c) 2006 Elsevier B.V. All rights reserved.